Clotrimazole Clotrimazole (BAY b 5097, FB 5097) alters the permeability of the fungal cell wall by inhibiting the biosynthesis of ergosterol, used in the treatment of fungal infections. In vitro
Clotrimazole causes a sustained depletion of intracellular Ca2+ stores, which results in activation of PKR, phosphorylation of eIF2alpha, and thereby in inhibition of protein synthesis at the level of translation initiation. Clotrimazole preferentially decreases the expression of the growth promoting proteins cyclin A, E and D1, resulting in inhibition of cyclin-dependent kinase activity and blockage of cell cycle in G1. Clotrimazole inhibits ADP-ribose-activated currents in HEK-293 cells expressing recombinant human TRPM2(hTRPM2). Clotrimazole (3 mM to 30 mM) produces an essentially complete inhibition of theTRPM2-mediated current. Clotrimazole antagonizes ADP-ribose-activated whole-cell and single-channel currents in the rat insulinoma cell-line CRI-G1. Clotrimazole (2 mM) causes a sharp decline in parasitemia, complete inhibition of parasite replication, and destruction of parasites and host cells within a single intraerythrocytic asexual cycle (approximately 48 hours). Clotrimazole effectively and rapidly inhibits parasite growth in five different strains of P. falciparum, in vitro, irrespective of their Chloroquine sensitivity.
In vivo
Clotrimazole stimulates a subset of capsaicin-sensitive and mustard oil-sensitive trigeminal neurons, and evoked nocifensive behavior and thermal hypersensitivity with intraplantar injection in mice. Clotrimazole-induced pain behavior is suppressed by the TRPV1-antagonist BCTC [(N-(-4-tertiarybutylphenyl)-4-(3-cholorpyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide)] and absent in TRPV1-deficient mice. Clotrimazole inhibits the cold and menthol receptor TRPM8, and blocks menthol-induced responses in capsaicin- and mustard oil-insensitive trigeminal neurons. Cell Data
